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Gram Positive Pathogens • • • • • Staphylococcus Streptococcus Enterococcus Listeria monocytogenes Bacillus anthracis A ‘coccus’ is a spherical bacteria Staphylococcus tend to cluster in groups While Streptococcus tend to line up in strings Gram-positive bacteria: Staphylococci Staphylococcus aureus Staphylococcus aureus causes a variety of suppurative (pus-forming) infections and toxinoses in humans. Important to distinguish Staphylococcus from Streptococcus • Most Staphylococcus are resistant to Penicillin G – Most produce a -lactamase – Or, may be resistant due to mutation of PBP (as in MRSA) • Most Streptococcus are susceptible to Penicillin G Lipoteichoic Acid also present As is Polysaccharide Capsule •Proteins that Disable Our Immune Defenses Include: •Protein A: Binds to IgG •Coagulase: leads to fibrin formation around bacteria, preventing phagocytosis •Hemolysins •Leukocidins •Penicillinase •Proteins that Tunnel Through Tissue Include: •Hyaluronidase: breaks down proteoglycans in connective tissue •Staphylokinase: Lyses formed fibrin clots •Lipase: Degrades the fat protective layer on surface of skin •Proease: Destroys tissue proteins •Exotoxins Produced Include: •Exfoliatin: causes skin to slough off (scalded skin syndrome) •Enterotoxins: cause food poisoning (vomiting and diarrhea) •Toxic Shock Syndrome Toxin (TSST-1): Causes massive T cell response and outpouring of cytokines, resulting in toxic shock syndrome. 3 Major Pathogenic Types of Staphylococcus: • Staphylococcus aureus – Many types of infections • Staphylococcus epidermidis – Most common cause of infection in indwelling prosthetic devices (prosthetic joints, heart valves, etc.) • Staphylococcus saprophyticus – Leading cause of urinary tract infections in sexually active young women Staphylococcal Scalded Skin Syndrome (SSSS) Staphylococcus causes superficial skin lesions such as boils, styes and furunculosis; Staphylococcus also causes more serious infections such as pneumonia, mastitis (inflammation of mammary gland), phlebitis (inflammation of vein, usually in leg), meningitis (inflammation of meninges), and urinary tract infections; Staphylococcus also causes deep-seated infections, such as osteomyelitis (inflammation of the bone) and endocarditis (inflammation of heart). S. aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and infections associated with indwelling medical devices. S. aureus causes food poisoning by releasing enterotoxins into food, and toxic shock syndrome by release of superantigens into the blood stream. Superantigens and TSS Toxic Shock Syndrome can occur via skin, vagina, or pharynx There has been some indication that it was associated with selected materials used in some ultra-abosorbant tampons. These materials are no longer used in the US. • http://highered.mcgrawhill.com/sites/0072556781/student_view0/chapte r32/animation_quiz_4.html Treatment of Infections Caused by Staphylococcus aureus • Antistaphylococcal penicillins: Nafcillin, oxacillin • First Generation cephalosporins: Cefazolin • Second Generation Cephalosporins: Cefuroxime • Third-generation cephalosporins: Ceftriaxone, cefotaxime, ceftizoxime -Lactam/ -lactamase inhibitor combinations: Ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanate • Carbapenems: Imipenem, meropenem Treatment of Infections Caused by Staphylococcus aureus (NOT methicillin resistant) Treatment of Methicillin-resistant Staphylococcus aureus • Vancomycin LINK Treatment of Methicillin-resistant Staphylococcus aureus • Linezolid Treatment of Methicillin-resistant Staphylococcus aureus • Streptogramins (Quinupristin-dalfopristin) Treatment of Methicillin-resistant Staphylococcus aureus • Daptomycin (cubicin) Treatment of Methicillin-resistant Staphylococcus aureus • Tigecycline (Tygacil) Doxycycline Gram-positive pathogens: Streptococcus pneumoniae Types of Streptococci • Group A beta-Hemolytic Streptococci – Streptococcal pharyngitis (Strep throat) – Streptococcal skin infections – Scarlet Fever – Streptococcal toxic shock syndrome – Rheumatic fever – Glomerulonephritis (inflammation of small blood vessels in the kidney) Streptococcus pyogenes Streptococcus pyogenes Impetigo Treatment of Streptococcus pyogenes + • Penicillin G • Aminopenicillins: Ampicillin • Aminoglycosides are sometimes added for synergy: Gentamicin Treatment of Streptococcus pyogenes + + • Clindamycin is added for severe invasive Streptococcus pyogenes infections Treatment for Penicillin-resistant Streptococcus pyogenes (and other penicillin resistant Streptococcus) • Vancomycin • Second-generation cephalosporins: Cefuroxime • Third-generation cephalosporins: cefotaxime, ceftriaxone Necrotizing Fasciitis • Necrotizing fasciitis is a rare condition, also known as flesheating bacterial disease, that is usually caused by streptococci, but can also be caused by staphylococci. • The disintegration of the skin tissue is due to the production of toxins, which may result in an overly-zealous response of the immune system. Types of Streptococci (Group B) • Viridans Group Streptococci – Dental Infections – Endocardidis Types of Streptococci (Group D) • Streptococcus pneumoniae S. pneumoniae is a common cause of otitis media (ear infection) and is also a major cause of bacterial pneumonia. Otitis media Streptococcus pneumoniae Treatment of Streptococcus pneumoniae Ampicillin • Penicillin G (high doses) • Aminopenicillins: Ampicillin (high doses) Treatment of Penicillin-resistant Streptococcus pneumoniae • Second Generation Cephalosoporins: Cefuroxime • Third Generation Cephalosporins: Cefotaxime, Ceftriaxone • Quinolones: Moxifloxacin, Levofloxacin • Vancomycin • Macrolides/ketolines: Telithromycin Enterococci Enterococcus Enterococci are gram positive cocci, that are normal residents of the GI tract • Two common species are Enterococcus faecalis and Enterococcus faecium. • In order of importance these microorganisms cause the following types of infections – Urinary Tract Infections (UTIs) – Intra - abdominal and intra - pelvic abscesses or postsurgery wound infections – Blood stream infections (BSIs) Enterococcus Resistance Mechanisms Treatment of Infections Caused by Enterococcus • • • • Penicillin G Aminopenicillins: Ampicillin Extended-spectrum Penicillins: Piperacillin Carbapenems: Imipenem, meropenem Treatment of Infections Caused by Enterococcus + • For serious infections, add an aminoglycoside for synergy: Gentamicin Treatment for Infections Caused by Penicillin-resistant Enterococci • Vancomycin Treatment for Vancomycin Resistant Enterococci (VRE) • Linezolid • Tetracycline-like: Tigecycline Gram-positive Bacteria: Listeria Monocytogenes • Listeria is a food-borne pathogen and is now recognized as a serious hazard by the food industry • Listeria can cause septicemia and meningitis • Listeria seems to particularly affect pregnant women, individuals with weakened immune systems, and newborns. Listeria monocytogenes • http://www.nature.com/nrmicro/animation/i mp_animation/index.html Treatment of Infections Caused by Listeria monocytogenes • Ampicillin + Gentamicin + • If penicillin allergic: – Trimethoprim-sulfamethoxazole Bacillus anthracis Bacillus anthracis LINK Bacillus anthracis Treatment of Infections Caused by Bacillus anthracis • Quinolones: Ciprofloxacin Treatment of Infections Caused by Bacillus anthracis • Tetracycline: Doxycycline Treatment of Infections Caused by Bacillus anthracis • For Inhalation Anthrax, a Second Agent Should be Added from the Following List: – – – – – – – – Rifampin Vancomycin Penicillin G Ampicillin Chloramphenicol Carbapenem: Imipenem Clindamycin Macrolide: Clarithromycin Gram-negative Bacteria: Enterobacteriaceae Septic Shock • Septic shock is a condition of hypotension (severely reduced blood pressure) caused by decreased tissue perfusion and oxygen delivery. • Septic shock can lead to multiple organ dysfunction syndrome and death, with the mortality rate approx. 50%. LINK Enterobacteriaceae • Escherichia coli • Salmonella • Shigella • Yersinia pestis • Klebsiella pneumoniae Escherichia coli Klebsiella Proteus Escherichia coli. • E. coli is a normal resident of the human intestinal tract and most strains are harmless. • However, some strains acquire the ability to produce toxins and to invade the blood stream. • Certain strains of E. coli., like serotype O157:H7, however, can cause serious illness. • E. coli is also a leading cause of urinary tract infections in women and also of meningitis in neonates. • Link • LINK • http://www.drkoop.com/animation /93/43.html Treatment of Infections Caused by: E. coli., K. pneumoniae, Proteus • Aminopenicillins: Ampicillin • First Generation Cephalosporins: Cefazolin • Sulfa drugs: Trimethoprimsulfamethoxazole • Quinolones: Ciprofloxacin, levofloxacin, moxifloxacin Treatment of Resistant Infections Caused by: E. coli., K. pneumoniae, Proteus • Third Generation Cephalosporins: Cefoxaxime, ceftriaxone, ceftizoxime • Monobactam: Aztreonam Treatment of Resistant Infections Caused by: E. coli., K. pneumoniae, Proteus • Extended Spectrum penicillins + -lactamase inhibitor: Piperacillin-tazobactam, ticarcillinclavulanate Treatment of Resistant Infections Caused by: E. coli., K. pneumoniae, Proteus Meropenem • Carbapenems: Imipenem, meropenem, ertapenem • Carbapenem + aminoglycoside in serious infections: Add Gentamicin, Tobramycin, amikacin Treatment of Infections Caused by: Enterobacter, Serratia, Citrobacter, Providencia, and Morganella Spp. • Carbapenems: Imipenem, meropenem, ertapenem • Sulfa Drugs: Trimethoprimsulfamethoxazole • Quinolones: Ciprofloxacin, levofloxacin • Fourth Generation Cephalosporins: Cefepime • + aminoglycoside: Gentamicin, tobramycin, amikacin Treatment of Infections Caused by: Salmonella enterica, Shigella spp. • Quinolones: Ciprofloxacin • Third-generation cephalosporins: Cefotaxime, ceftriaxone, ceftizoxime • Macrolides: Azithromycin Treatment of Infections Caused by: Yersinia spp. LINK Historical Link Treatment of Infections Caused by: Yersinia spp. Gentamycin • Aminoglycosides: Gentamicin, streptomycin Treatment of Infections Caused by: Yersinia spp. • Tetracyclines: Doxycycline Treatment of Infections Caused by: Yersinia spp. •Quinolones: Ciprofloxacin •Sulfa drugs Gram-negative Bacteria: Pseudomonas Pseudomonas Pseudomonas aeruginosa Resistance of Pseudomonas Treatment of Infections caused by Pseudomonas aeruginosa • • • • • • • Extended spectrum penicillins: Piperacillin, Ticarcillin Third Generation Cephalosporins: Ceftazidime Fourth-generation Cephalosporins: Cefepime Carbapenems: Imipenem, meropenem Monobactams: Aztreonam Quinolones: Ciprofloxacin, Levofloxacin Aminoglycosides: Gentamicin, tobramycin, amikacin Treatment of Serious Infections Caused by Pseudomonas aeruginosa • Antipseudomonal -lactam + aminoclycoside: Ceftazidime + Tobramycin Treatment of Serious Infections Caused by Pseudomonas aeruginosa • Extended-spectrum penicillin + antipseudomonal quinolone: Piperacillin + Ciprofloxacin Neisseria Neisseria meningitidis • The meninges are a series of membranes surrounding the central nervous system • They consist of three layers: the dura matter, the arachnoid matter, and the pia matter Neisseria meningitidis Neisseria meningitidis Neisseria gonorrhoeae Neisseria gonorrhoeae Treatment of Infections Caused by Neisseria meningitidis • Penicillin G • Third generation cephalosporins: Ceftriaxone, cefotaxime • Chloramphenicol Treatment of Infections Caused by Neisseria Gonorrhoeae • Third Generation Cephalosporins: Ceftriaxone, cefixime Curved Gram Negative Bacilli – Campylobacter jejuni, – Helicobacter pylori, – Vibrio cholerae Campylobacter jejuni Camphylobacter jejuni is a common cause of gastroenteritis. Campylobacter jejuni Treatment of Infection Caused by Campylobacter jejuni Azithromycin • Macrolides: Erythromycin, azithromycin, clarithromycin • Link Treatment of Infection Caused by Campylobacter jejuni • Quinolones: Ciprofloxacin Helicobacteri pylori Helicobacter pylori Helicobacter pylori Duodenal Peptic Ulceration Caused by Helicobacter pylori Treatment of Infection Caused by Helicobacter pylori • Amoxicillin + clarithromycin + proton pump inhibitor • Metronidazole + clarithromycin + proton pump inhibitor • Bismuth subsalicylate + metronidazole + tetracycline + proton pump inhibitor Vibrio cholerae LINK Vibrio cholerae • Cholera is a bacterial infection of the small intestine. • Cholera is spread by eating or drinking contaminated water or food. Vibrio cholerae The main symptoms of cholera are watery diarrhea and vomiting, which can lead to rapid dehydration and death. Treatment of Infection Caused by Vibrio cholerae • Tetracyclines: tetracycline, doxycycline • Sulfa drugs: Trimethoprimsulfamethoxazole • Quinolones: Ciprofloxacin • Macrolides: Erythromycin, Azithromycin Haemophilus influenzae Haemophilus influenzae •Haemophilic means ‘blood loving’. The organism requires a blood-containing medium for growth •Influenzae: The bacterium often attacks the lungs of a patient with viral influenza. • Since the organism was frequently isolated from the lungs of patients during the 1890 and 1918 influenza pandemics, scientists incorrectly concluded that the bacterium was the causative agent. Haemophilus influenzae Haemophilus influenzae Treatment of Infections Caused by Haemophilus influenzae • Aminopenicillins + -lactamase inhibitor: – Amoxicillin/clavulanate – Ampicillin/sulbactam • Second-generation cephalosporin – Cefuroxime • Third-generation cephalosporin – Ceftriaxone – Cefotaxime Bordetalla pertussis • Bordetalla pertussis causes a violent cough called ‘whooping cough’ • Bordetalla pertussis Bordetella pertussis LINK Treatment of Infection Caused by Bordetella pertussis • Macrolides: Azithromycin, Clarithromycin, Erythromycin Moraxella catarrhalis • Causes otitis media, pneumonia, and sinusitis • Usually produces -lactamase Treatment of Infections Caused by Moraxella catarrhalis • Extended spectrum penicillins: piperacillin, ticarcillin -lactam/-lactamase inhibitor combinations: piperacillin/tazobactam, ticarcillin/clavulanate • Second and third-generation cephalosporins Acinetobacter • Recent outbreak among soldiers in Iraq • Second leading cause of infection among troops during the Vietnam conflict Acinetobacter Treatment of Infection Caused by Acinetobacter • Sulbactam • Carbapenems • Quinolones Anaerobic Bacteria Gram positive: Clostridia spp. Clostridium tetani • Clostridium tetani is the etiologic agent of tetanus • Characterized by persistent tonic spasm, usually involving the masseter muscles (lockjaw) • Usually caused by deep wound becoming infected with C. tetani spores. Clostridium botulinum • Clostridium botulinum is usually acquired by ingestion of food contaminated with C. botulinum spores • Botulinum toxin leads to cranial neuroopathies and weakness rather than muscular spasm. • Link • LINK Botulinum Toxin (Botox) • Botulinum toxin is a neurotoxic protein produced by Clostridium botulinum • It was discovered in the 1950’s that injecting small amounts decreased muscle activity by blocking release of acetylcholine at the neuromuscular junction Botulinum Toxin (Botox) LINK LINK LINK LINK Treatment of Infections Caused by Clostridium spp. • Penicillin G • Metronidazole (may be associated with better outcomes) Clostridium difficile Clostridium difficile LINK Treatment of Infections Caused by Clostridium difficile • Oral metronidazole • Oral vancomycin Clostridium perfringens is the cause of gas gangrene Gas Gangrene • Gangrene comes from the Greek ‘gangraina’ meaning ‘putrefication of tissues’ • Dry gangrene often occurs in the toes and feet of elderly patients • Wet gangrene occurs in naturally moist tissues, such as the mouth, bowel, lungs. • Gas gangrene is due to infection by Clostridium perfringens, which produces gas within the tissues. • Such gas-producing infection spreads very rapidly, and should be considered a medical emergency. Treatment of Infections Caused by Clostridium perfringens • Penicillin + one of the following: – Clindamycin – Tetracycline – Metronidazole Hyperbaric Oxygen Therapy One treatment for gas gangrene includes hyperbaric oxygen therapy Anaerobic Gram-negative Bacteria Common Anaerobic Gram-negative Pathogens • Bacteroides fragilis – Usually produces -lactamase • Prevotella • Porphyromonas Treatment of Anaerobic Gramnegative Infections -lactam/-lactamase inhibitor combinations – Ampicillin-sulbactam – Piperacillin-tazobactam – Ticarcillin-clavulanate • Carbapenems: Imipenem, Meropenem, Ertapenem • Metronidazole Atypical Bacteria: Chlamydia Chlamydia trachomatis • One of the most common sexually transmitted diseases • Also a leading cause of blindness in some parts of the world • LINK Chlamydia is a bacterial infection of the genital tract spread through sexual contact. If untreated, it can result in various medical complications, including damage to the reproductive organs. The disease affects both women and men, although reported cases for women greatly exceed those for men. Chlamydia affects people in all age groups, but it is particularly prevalent among teenagers and young adults. According to the U.S. Centers for Disease Control and Prevention (CDC), the infection is most prevalent among women aged 20 to 25. Chlamydia trachomatis Some signs and symptoms that may be present in people infected with chlamydia are: • • • • • • • • • • Abnormal discharge from the penis or vagina Burning sensation during urination Lower abdominal or back pain Nausea Fever Pain during intercourse Burning or itching around the head of the penis Swollen or tender testicles Bleeding between menstrual cycles Proctitis (inflammation of the rectum) Life Cycle of Chlamydia trachomatis Link USMLE Study Song Treatment of Infections Caused by Chlamydia trachomatis • Tetracyclines – Tetracycline – Doxycycline • Macrolides – Azithromycin – Erythromycin – Telithromycin • Quinolones – Ofloxacin – Moxifloxacin – Gemifloxacin Mycoplasma pneumoniae Mycoplasma pneumoniae Treatment of Infections Caused by Mycoplasma pneumoniae • Macrolides: Azithromycin, clarithromycin, erythromycin telithromycin • Tetracyclines: Tetracycline, doxycycline • Quinolones: Levofloxacin, moxifloxacin, gemifloxacin Atypical Bacteria: Legionella • Legionella pneumophila is the most common species, and is the causative agent of Legionaires’ disease • Once in the lung, Legionella organisms are taken up by macrophages and multiply within them. Legionalla pneumophila • http://www.natur e.com/nrmicro/a nimation/imp_an imation/index.ht ml Treatment of Infections Caused by Legionella pneumophila • Macrolides: Azithromycin • Quinolones: Levofloxacin, moxifloxacin Brucella • Brucellosis is a disease of animals, that is occasionally transmitted to humans • Contact with animals and/or ingestion of unpasteurized milk or cheese are risk factors Brucella Brucella Treatment of Infections Caused by Brucella spp. + • Doxycycline + rifampin • Doxycycline + gentamicin • Doxycycline + streptomycin Francisella tularensis Tularemia is contracted by contact with infected animals (squirrels) or through an arthropod vector (fleas, ticks, etc.) Francisella tularensis Treatment of Infections Caused by Francisella tularensis • Aminoglycosides: Streptomycin, Gentamicin • Tetracyclines: Tetracycline, doxycycline Rickettsia spp Rickettsia rickettsii Rocky Mountain spotted fever is the most severe and most frequently reported rickettsial illness in the United States. The disease is caused by Rickettsia rickettsii, a species of bacteria that is spread to humans by ixodid (hard) ticks. Treatment of Infections Caused by Rickettsia spp. • Tetracyclines – Doxycycline – Tetracycline Spirochetes: Treponema pallidum Treponema pallidum LINK Treponema pallidum Treponema pallidum LINK Treatment of Infections Caused by Treponema pallidum • Penicillin G (including benzathine penicillin) • Tetracyclines • Third Generation Cephalosporins Penicillin procaine Penicillin benzathine These particular salts of penicillin are injected intramuscularly and absorbed slowly over a period of time. Penicillin G benzathine Procaine penicillin G http://www.chemblink.com/products/54-35-3.htm Borrelia borgdorferi Borrelia burgdorferi Borrelia burgdorferi is the causative agent of Lyme Disease Treatment of Infections Caused by Borrelia burgdorferi • Tetracyclines: Doxycycline • Aminopenicillins: Amoxicillin Leptospira interrogans Leptospira interrogans Treatment of Infection Caused by Leptospira interrogans • Tetracyclines: Doxycycline • Aminopenicillins: Amoxicillin • Severe Disease can be treated with Penicillin G, Ampicillin, or Ceftriaxone Mycobacteria • Mycobacterium tuberculosis • Mycobacterium avium complex • Mycobacterium leprae Mycobacterium tuberculosis Link Mycobacterium tuberculosis Mycobacterium tuberculosis Treatment of Infections Caused by Mycobacterium tuberculosis • Active Disease – Isoniazid + Rifampin + Pyrazinamide + Ethambutol for two months – Followed by: Isoniazid + Rifampin for Four months • Latent Disease – Isoniazid for 9 months Mycobacterium avium complex Mycobacterium avium complex Treatment of Infections Caused by Mycobacterium avium complex (MAC) • Clarithromycin + ethambutol + rifabutin Mycobacterium leprae Mycobacterium leprae Leprosy Treatment of Infections Caused by Mycobacterium leprae • Dapsone + rifampin + clofazimine